The overall focus of the Einstein Aging Study (EAS) is to identify the earliest cognitive, metabolic, anatomic, and neuropathologic markers that distinguish 'normal aging' from dementia in a large community-based sample. Cognitive decline can be described in three clinical stages: cognitive stability, cognitive impairment, and dementia. The stage of cognitive impairment represents a group at elevated risk for subsequent dementia. The EAS proposes to apply operational definitions of Amnestic Cognitive Impairment (ACI) that identify individuals at high risk for Alzheimer's Disease (AD) and Alzheimer's Disease with Vascular Dementia (AD/VaD) significantly earlier than current standard definitions such as Mild Cognitive Impairment (MCI). On a long-term basis, the EAS will reduce the burden of dementia by facilitating earlier and more accurate detection, identification of remediable risk factors, and a better understanding of the underlying biological processes. Supported by four Cores, the three integrated projects will address the following issues: Project 1 (Risk Factors and Stages of Cognitive Decline) will quantify the rate of transition and identify risk factors and neuroimaging markers for transitions from "normal aging" to ACI and NACI, and from these states to Alzheimer's disease and AD/VaD. Project 2 (Memory Mechanisms of Aging, Preclinical and Early Dementia) will apply novel methods to study how measures of processing speed and intra-individual variability may improve detection of preclinical dementia beyond standard methods that consider only level of cognitive performance. Project 3 (Clinico-Pathologic Correlations in Aging and Dementia) will examine structural and biochemical changes in the human brain in aging and AD, particularly focusing on differences in synthesis and degradation of amyloid in intermediate stages and AD, on the correlations of tau pathology with cognitive impairment, and on structural indices for vascular dementia. Common research themes, a shared participant sample and shared resources of the cores link these projects, The ability to address important research questions will be enhanced by the ability to combine detailed risk factor assessments (Project 1) with in-depth cognitive measures (Project 2) and with neuropathological variables (Project 3). Together, these projects will contribute to the understanding of the natural history of dementia, and of mechanisms which underlie transitions across stages of cognitive decline.